Low-dose capsaicin decreases lung ischemia-reperfusion injury and underlying mechanism in rats

Abstract

To explore the effects of low-dose capsaicin (CAP) on lung ischemia-reperfusion (IR) injury and elucidate its possible mechanisms in rats. A total of 32 Sprague-Dawley rats were randomly divided into 4 groups of S (sham thoracotomy and mechanical ventilation for 5.0 h), IR (an occlusion of left pulmonary hilus for 1.0 h followed by reperfusion for 4.0 h), CAP (an injection of CAP at 5.0 min pre-occlusion) and CGRP8-37 group (an injection of CGRP receptor antagonist CGRP8-37 at 10.0 min pre-occlusion followed by the same treatment as CAP group) (n = 8 each). At pre-occlusion, 0.5 h and 4.0 h post-reperfusion, blood samples were collected for blood gas analyses and arterial oxygen pressure (PaO2) and alveolar arterial oxygen difference (A-aDO2) measured. At the end of experiment, lung tissues were obtained to measure the level of tumor necrosis factor alpha (TNF-α), lung tissue wet to dry weight ratio (W/D) and lung histological changes. At 0.5 h post-reperfusion, PaO2 in S group was significantly higher than that in IR, CAP and CGRP8-37 groups ((147.7±32.4) vs (100.8±18.9), (123.9±16.3), (121.0±15.2) mmHg (1 mmHg=0.133 kPa), all P<0.05) and it was higher in CAP group than in IR group (P<0.05); A-aDO2 increased in IR and CGRP8-37 groups versus S group ((151.5±21.9), (134.3±15.1) vs (118.4±19.1) mmHg, both P<0.05). At 4 h post-reperfusion, PaO2 was higher in CAP group than those in IR and CGRP8-37 groups ((146.0±21.1) vs (113.5±21.1), (124.0±16.4) mmHg, both P<0.05). And A-aDO2 in CAP group was lower than those in IR and CGRP8-37 groups ((111.4±23.4) vs (140.8±22.0), (132.7±16.4) mmHg, both P<0.05); the level of TNF-α in CAP group was lower than that in IR group ((2.7±0.9) vs (3.7±1.1) pg/mg, P<0.05); W/D ratios were remarkably higher in IR, CAP and CGRP8-37 groups than that in S group (5.74±0.52, 6.03±0.78, 5.26±0.24 vs 4.87±0.34, all P<0.05), and it was lower in CAP group than in CGRP8-37 group (P<0.05). Under light microscope, the pathological lesions were more severe in IR and CGRP8-37 groups than those in CAP group at 4 h post-reperfusion. Low-dose capsaicin exerted protective effects on lung ischemia reperfusion injury in rats. And it is mediated partially by calcitonin gene-related peptide receptor. The underlying molecular mechanism is involved in suppressed inflammatory response.